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Open Access Research article

Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

Antonio López-Vázquez1, Lourdes Mozo1, Rebeca Alonso-Arias1, Beatriz Suárez-Álvarez1, José Ramón Vidal-Castiñeira1, Eduardo Arranz2, Umberto Volta3, Carlos Bousoño5, Marcos López-Hoyos67, Luís Rodrigo4 and Carlos López-Larrea17*

Author Affiliations

1 Department of Immunology, Hospital Universitario Central de Asturias, Oviedo 33006, Spain

2 Mucosal Immunology Laboratory, Department of Paediatrics and Immunology-IBGM, University of Valladolid, Valladolid, Spain

3 Department of Gastroenterology and Internal Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

4 Department of Gastroenterology, Hospital Universitario Central de Asturias, Oviedo, Spain

5 Department of Paediatrics, Hospital Universitario Central de Asturias, Oviedo, Spain

6 Department of Immunology, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain

7 Fundación Renal “Iñigo Álvarez de Toledo”, Madrid, Spain

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BMC Medicine 2014, 12:34  doi:10.1186/1741-7015-12-34

Published: 25 February 2014

Abstract

Background

Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes.

Methods

We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies.

Results

Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without.

Conclusions

The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones.

Keywords:
Autoantibodies; Autoimmune diseases; Celiac disease; MICA; NKG2D; Type 1 diabetes mellitus